Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
J Cell Mol Med. 2019 May;23(5):3417-3428. doi: 10.1111/jcmm.14237. Epub 2019 Feb 19.
Diabetic nephropathy (DN) is characterized by inflammation of renal tissue. Glomerular endothelial cells (GEnCs) play an important role in inflammation and protein leakage in urine in DN patients. Chemerin and its receptor ChemR23 are inducers of inflammation. The aim of this study was to investigate the function of chemerin/ChemR23 in GEnCs of DN patients. Immunohistochemical staining and qRT-PCR were used to measure the expression of chemerin, ChemR23 and inflammatory factors in renal tissues of DN patients. Db/db mice were used as animal model. ChemR23 of DN mice was knocked down by injecting LV3-shRNA into tail vein. Inflammation, physiological and pathological changes in each group was measured. GEnCs were cultured as an in vitro model to study potential signalling pathways. Results showed that expression of chemerin, ChemR23 and inflammatory factors increased in DN patients and mice. LV3-shRNA alleviated renal damage and inflammation in DN mice. GEnCs stimulated by glucose showed increased chemerin, ChemR23 and inflammatory factors and decreased endothelial marker CD31. Both LV3-shRNA and SB203580 (p38 MAPK inhibitor) attenuated chemerin-induced inflammation and injury in GEnCs. Taken together, chemerin/ChemR23 axis played an important role in endothelial injury and inflammation in DN via the p38 MAPK signalling pathway. Suppression of ChemR23 alleviated DN damage.
糖尿病肾病(DN)的特征是肾组织炎症。肾小球内皮细胞(GEnC)在 DN 患者的炎症和尿蛋白漏出中起重要作用。趋化素及其受体 ChemR23 是炎症的诱导物。本研究旨在探讨趋化素/ChemR23 在 DN 患者 GEnC 中的功能。免疫组织化学染色和 qRT-PCR 用于测量 DN 患者肾组织中趋化素、ChemR23 和炎症因子的表达。使用 Db/db 小鼠作为动物模型。通过尾静脉注射 LV3-shRNA 敲低 DN 小鼠的 ChemR23。测量每组的炎症、生理和病理变化。将 GEnC 培养为体外模型,以研究潜在的信号通路。结果表明,DN 患者和小鼠中趋化素、ChemR23 和炎症因子的表达增加。LV3-shRNA 减轻了 DN 小鼠的肾损伤和炎症。葡萄糖刺激的 GEnC 显示趋化素、ChemR23 和炎症因子增加,内皮标记物 CD31 减少。LV3-shRNA 和 SB203580(p38 MAPK 抑制剂)均可减弱 GEnC 中趋化素诱导的炎症和损伤。总之,趋化素/ChemR23 轴通过 p38 MAPK 信号通路在 DN 中的内皮损伤和炎症中起重要作用。抑制 ChemR23 可减轻 DN 损伤。